The present invention is directed to a method and apparatus for delivering medication over a prolonged period. The method included charging or recharging an implanted device which has been or can be impregnated with a bioactive ingredient without the requirement for removing the device from the body.
It has become common to treat a variety of medical conditions by temporarily or permanently introducing an implantable medical device partly or completely into the esophagus, trachea, colon, biliary tract, urinary tract, vascular system, or other locations within a human or veterinary patients. Many treatments of the vascular or other systems entail introducing a device such as a stent, a catheter, a balloon, a wire guide, a cannula, or the like.
Some drawbacks can be encountered during use of a stent or other implantable medical device. For example, when a device is introduced into and manipulated through the vascular system of a patient, the blood vessel walls can be disturbed or injured. Clot formation or thrombosis often results at the injured site, causing stenosis (closure) of the blood vessel. Moreover, if the medical device is left within the patient for an extended period of time, thrombus often forms on the device itself, again causing stenosis. As a result, the patient is placed at risk of a variety of complications, including heart attack, pulmonary embolism, and stroke. Thus, the use of such a medical device can entail the risk of precisely the problems that its use was intended to ameliorate.
The efficacy of a stent can be assessed by evaluating a number of factors, such as thrombosis, neotimimal hyperplasia, smooth muscle cell migration and proliferation following implantation of the stent, injury to the artery wall, overall loss of luminal patency, stent diameter in vivo, thickness of the stent, and leukocyte adhesion to the luminal lining of tented arteries. However, the chief areas of concern are early subacute thrombosis and eventual restenosis of the blood vessel due to intimal hyperplasia.
Other conditions and diseases are treatable with stents, catheters, cannulae, and other medical devices inserted into the esophagus, trachea, colon, biliary tract, urinary tract, and other locations in the body. A wide variety of bioactive materials, including drugs, therapeutic agents, diagnostic agents, and other materials having biological or pharmacological activity within a patient, have been applied to such medical devices for the purpose of introducing such materials into the patient. Unfortunately, the durable application of bioactive materials to these medical devices and the like, sufficient for such introduction to occur, is often problematic. A range of impregnated or layered materials have been applied to such devices to permit the timed release of bioactive materials from such devices, or even to permit bioactive materials to be applied to such devices at all. Therapeutic pharmacological agents have been developed to improve successful placement of the medical device as well as to be delivered to the site of device implantation. Among the drugs that can be delivered via impregnated or loaded medical devices are those that can treat restenosis, tissue inflammation, promote endotheliazation or any other disease that may inhibit the successful implantation and retention of the device.
Implantable devices made of biologically acceptable metals were previously unable to deliver localized bioactive materials to tissues at the location treated by the device. However, there are polymeric materials that can be loaded with and release bioactive materials, including drugs or other pharmacological treatment, which can be used for drug delivery.
Yan, in U.S. Pat. No. 5,843,172, the entire contents of which are hereby incorporated by reference, describes a stent made of metal which has porous cavities in the metallic portion of the stent so that the drugs can be loaded directly into the pores without substantially weakening the structural and mechanical characteristics of the prosthesis. However, once the bioactive material has been depleted from the stent, if it is still necessary to deliver the material to the site of the stent, the stent must be replaced.
It is an object of the present invention to overcome the aforesaid deficiencies in the prior art.
It is another object of the present invention to provide an implantable device which can be recharged with a bioactive material.
It is a further object of the present invention to provide an implantable device which can be charged with a bioactive material.
According to the present invention, an implantable device such as a stent is provided which is capable of holding an induced charge of sufficient magnitude that the device may, by electrostatic means, attract bioactive material to itself. The charge, either positive or negative, or relative to the bioactive material sufficiently positive or negative, is deposited into the implantable device via an exterior induction coil. The implantable device itself becomes an introduced xe2x80x9cdosage formxe2x80x9d, becoming part of a biologically closed electric circuit, as shown in Nordenstrom, B. E., Biologically Closed Electrical Systems; Stockholm, Nordic Medical Publications, 1983. This mechanism is similar to that described in Sceusa, U.S. Pat. No. 6,414,033, the entire contents of which are hereby incorporated by reference.
The bioactive ingredient, which may be in ionic form as described in Sceusa, supra, or in a neutral complex that will dissociate tonically in the presence of the charge of the implantable device, will then attach itself to the implantable device.
The implantable device must possess the correct electronic transfer system to permit an induced charge to form, to be carried, and to be retained long enough to act electrostatically and attract the medication to itself. Many materials having these properties are known, including plastics and ceramics which have metal atoms covalently bonded into the matrix, or an entirely ceramic material without metal ions, having the correct electronic transfer system. Alternatively, the implantable device can be made with a metallic or capacitive strip entirely embedded within the device to drive the accretion of medication into the matrix of the device. In yet another embodiment, the implantable device can be made of porous metal, such as disclosed in Yan, U.S. Pat. No. 5,843,172. Any conventional physiologically acceptable material which has the needed electron transfer (capacitance) systems can be used in the present invention.
To recharge or charge the implantable device, the bioactive material can be delivered intravenously or trans-membrane by one of two systems:
1. Intravenous injection, which is minimally invasive; or
2. Teorell-Meyer dosage or xe2x80x9creversexe2x80x9d Teorell-Meyer forms, depending upon the anatomy and location of the implantable medical device.
The bioactive material should be in a xe2x80x9creversexe2x80x9d Teorell-Meyer dosage form as follows:
1. It may be a neutral complex of the bioactive ingredient and a suitable carrier molecule, or a synthetic carrier molecule, such that the Kd (the constant of dissociation), which is the reciprocal of the Ka (constant of association), is less than the electrostatic force of attraction exerted by the implantable device for the bioactive material. Thus, the medication will leave the carrier molecule and become embedded in the implantable device.
2. The bioactive ingredient may be a stable charged complex with a direct attraction for the charge in the implantable device.